28593-24-0Relevant academic research and scientific papers
N-Acylethoxymethylene hydrazones as the source of a C1 fragment
Kocevar,Susin,Polanc
, p. 773 - 774 (1993)
The title compounds were found to be efficient reagents for the ring closure of the appropriate hydrazines or o-phenylenediamine. A new C = C bond was formed on their reaction with 1,3-dimethylbarbituric acid.
Optimization of the Urea Linker of Triazolopyridazine MMV665917 Results in a New Anticryptosporidial Lead with Improved Potency and Predicted hERG Safety Margin
Oboh, Edmund,Schubert, Tanner J.,Teixeira, Jose E.,Stebbins, Erin E.,Miller, Peter,Philo, Emily,Thakellapalli, Haresh,Campbell, Scott D.,Griggs, David W.,Huston, Christopher D.,Meyers, Marvin J.
, p. 11729 - 11745 (2021/08/24)
Cryptosporidiosis is caused by infection of the small intestine by Cryptosporidium parasites, resulting in severe diarrhea, dehydration, malabsorption, and potentially death. The only FDA-approved therapeutic is only partially effective in young children and ineffective for immunocompromised patients. Triazolopyridazine MMV665917 is a previously reported anti-Cryptosporidium screening hit with in vivo efficacy but suffers from modest inhibition of the hERG ion channel, which could portend cardiotoxicity. Herein, we describe our initial development of structure-activity relationships of this novel lead series with a particular focus on optimization of the piperazine-urea linker. We have discovered that piperazine-acetamide is a superior linker resulting in identification of SLU-2633, which has an EC50 of 0.17 μM, an improved projected margin versus hERG, prolonged pharmacokinetic exposure in small intestine, and oral efficacy in vivo with minimal systemic exposure. SLU-2633 represents a significant advancement toward the identification of a new effective and safe treatment for cryptosporidiosis.
ARYLACETAMIDE ANALOGS OF PIPERAZINE-[1,2,4]TRIAZOLO[4,3-B]PYRIDAZINES
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Paragraph 0092; 0094, (2021/12/31)
Provided are compounds with the following structure: Formula (I), and methods of making and using same. The methods of using the compounds may be methods for treating or prophylaxis of a cryptosporidium infection.
Synthesis and antiproliferative activity of 2-(([1,2,4]triazolo[4,3-b]- pyridazin-6-yloxy)methyl)-2,4-dimethyl-3,4-dihydro-2Hbenzo[b][1,4]oxazine derivatives
Ilic, Milos,Ilas, Janez,Liekens, Sandra,Matyus, Peter,Kikelj, Danijel
scheme or table, p. 298 - 311 (2011/12/15)
A small library of [1,2,4]triazolo[4,3-b]pyridazin-6-yloxy derivatives 14-17 of N-benzyl-N-(2-((4-amidinophenoxy)methyl)-2,4-dimethyl-3,4-dihydro-2H- benzo[b][1,4]oxazin-7-yl)-oxalic acid monoamides 1 was prepared by replacement of benzamidine with a [1,2
TRIAZOLOPYRIDAZINE DERIVATIVES HAVING INHIBITORY ACTIVITY AGAINST ACETYL-COA CARBOXYLASE
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Page/Page column 9-10; 24, (2008/12/06)
The present invention relates to a novel triazolopyridazine derivative or a pharmaceutically acceptable salt thereof, and an Acetyl-CoA Carboxylase2 (ACC2) comprising same as an active ingredient. The triazolopyridazine derivative of the present invention
Triazolo- and tetrazolopyridazine derivatives and their hypotension and heart rate activity
Katrusiak,Melzer,Baloniak,Bobkiewicz,Polcyn
, p. 217 - 223 (2007/10/03)
6-Chloro-, 6-morpholino- and 6-N-methylpiperazino-1,2,4-triazolo[4,3-b]- or 1,2,3,4-tetrazolo [1,5-b]pyridazines [II-VII] were synthesized from 3-chloro-6-hydrazinopyridazine [I]. Positive effect of a series of tetra- and triazolopyridazines for lowering blood-pressure without affecting the heart rate was found in tests on rats. Their lipophilicity and other properties are discussed.
Synthesis of [1,2,4]triazolo[4,3-b]pyridazine-3-carboxylic acids
Kosary, Judit
, p. 451 - 454 (2007/10/03)
The first synthesis of 6-substituted-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylic acids 2a-c was carried out by an enzymatic hydrolysis of alkyl 6-substituted-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylates 1 by α-chymotrypsin (EC 3.4.21.1) immobilized on a polyacrylamide-type bead support (ACRYLEX C-100). Earlier the synthesis of these compounds failed owing to ready decarboxylation of the products. During enzymatic hydrolysis decarboxylation was only a side reaction.
NMR spectroscopic investigations with ethyl 1-(hetero)aryl-5-hydroxy-1H-pyrazole-4-carboxylates.
Holzer, Wolfgang,Schmid, Eva
, p. 1341 - 1350 (2007/10/02)
The synthesis of a series of ethyl N-1-(hetero)aryl-5-hydroxy-1H-pyrazole-4-carboxylates by reaction of diethyl ethoxymethylenemalonate with appropriate hydrazines is described.According to nmr-spectroscopic investigations (1H- and 13C-nmr) the title compounds exist as 5-hydroxy tautomers in deuteriochloroform as well as in deuteriodimethyl sulfoxide solution.
Synthesis and Reactivity of some 1,2,4-Triazolopyridazine Derivatives
Baloniak, S.,Katrusiak, A.
, p. 683 - 692 (2007/10/02)
The triazolopyridazine derivatives were obtained in the reaction of 3-chloro-6-hydrazinopyridazine with acetic acid and ethyl chloroformate.Acting on 6-chloro-3-methyl-1,2,4-triazolopyridazine with phosphorus pentachloride, a methyl group in position 3 has unexpectedly been exchanged by chlorine.The mechanism of fusing the triazole ring to the pyridazine system has been studied by the reaction of 3-chloro-6-hydrazinopyridazine with formaldehyde, acetaldehyde, and treatment the resulting Schiff bases by bromine in acetic acid with sodium acetate added.Key words: 1,2,4-Triazolopyridazines, nucleophilic substitution, cyclization mechanism
NOUVEAUX DERIVES PYRIDAZINIQUES ET PHTALAZINIQUES DOUES D'ACTIVITE PHYSIOLOGIQUE
Caprosu, Maria,Stefanescu, Eugenia,Ungureanu, Margareta,Petrovanu, Magda
, p. 657 - 664 (2007/10/03)
This paper reports eleven new pyridazines and phthalazines derivatives. Products 5-11 have been obtained starting from 3-chloro-6-hydrazino-pyridazine (4), by means of various reactions. Products 14-16 belong to the class of phthalazinium-ylids. The biolo
